Download 3-in-1: A novel approach to study membrane protein pharmacology

3-in-1: A novel approach to study membrane protein pharmacology
Membrane proteins make up about 25% of all proteins encoded by the human genome and are considered
major drug targets. One type of membrane protein, the family of ligand-gated ion channels (LGICs),
mediates crucial functions in the nervous system and has been implicated a numerous diseases. Most LGICs
are molecular assemblies of more than one subunit, but conventional methods to study these proteins
cannot easily address the contribution of individual subunits within such a protein complex. Recent
advances in the field of molecular biology and chemical biology now allow to overcome this limitation
by using of inteins, a family of self-splicing proteins, to link together individual subunits into one large
protein containing all subunits required for full LGIC assembly and function. This will allow us to individually
manipulate a defined number of subunits within LGIC complexes and therefore enable us to elucidate
the function and pharmacology of these medically relevant proteins in unprecedented detail.
Fig 1: Left: Example of the structure of a trimeric LGIC with subunits indicated by different colors and the ligand shown in red ; Right: cartoon
illustrating the use of (split)inteins in order to create a trimeric protein in which a defined number of subunits can be individually manipulated.
The development of such a cutting-edge approach will be broadly applicable to numerous types of proteins
and will no doubt provide the foundation of many future studies in different fields.
The project will be carried out in the newly-established Center for Biopharmaceuticals, which provides stateof-the-art facilities and a very vibrant and international environment. The project will be supervised by Assoc.
Prof. Stephan A. Pless ([email protected]). For more information please contact us or visit our
website: www.theplesslab.com